biostudies-literatureHu SNational Science and Technology Major Projecte70153https://www.ebi.ac.uk/biostudies/studies/S-EPMC12408367biostudies-literatureUnknown14(9)Tumour progression depends on the bidirectional interactions between cancer and stroma in the heterogeneous tumour microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumour survival under starvation is poorly defined. Here, we identify cancer cells selectively secrete miR-33a with the assistance of aconitase 1 (ACO1), an iron-responsive RNA binding protein, under glucose starvation and lower iron level, which affiliates the binding capability of miR-33a and ACO1. Exosomal miR-33a suppresses putrescine biosynthesis by targeting AGMAT in cancer-associated fibroblasts (CAFs) from tumour core region, where putrescine inhibits the expression of demethylase KDM5C. TIA1 gene, stress granule (SJournal of extracellular vesiclesCancer Cell-Secreted miR-33a Reduces Stress Granule Formation by Targeting Polyamine Metabolism in Stroma to Promote Tumourigenesis.PMC124083672021YFA0804803Wu JHu SWu MLi JWang CFu XChen MDeng GLi LLi MYan WZhao XLi XLi ZHuang WZhang XHua AHu QZhou HfalseCancer Cell-Secreted miR-33a Reduces Stress Granule Formation by Targeting Polyamine Metabolism in Stroma to Promote Tumourigenesis.Tumour progression depends on the bidirectional interactions between cancer and stroma in the heterogeneous tumour microenvironment (TME) partially through extracellular vesicles (EVs). However, the secretary mechanism and biological effect of cancer cell derived EVs on tumour survival under starvation is poorly defined. Here, we identify cancer cells selectively secrete miR-33a with the assistance of aconitase 1 (ACO1), an iron-responsive RNA binding protein, under glucose starvation and lower iron level, which affiliates the binding capability of miR-33a and ACO1. Exosomal miR-33a suppresses putrescine biosynthesis by targeting AGMAT in cancer-associated fibroblasts (CAFs) from tumour core region, where putrescine inhibits the expression of demethylase KDM5C. TIA1 gene, stress granule (S2025-01-01T00:00:00Z2025 Sep2026-05-29T22:38:54.879Z2026-04-08T06:18:47.898ZS-EPMC124083674090382610.1002/jev2.70153